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Biological cause of cancer

Cancer is not one disease it’s actually a hundred of diseases and even in one cell type in the body. Our body is composed of 206 cell type and even in one cell type you have multiple types of cancers, thus, you hundred types of cancer.

It’s like the whole constellation of diseases. The first information about cancer came back several years ago. Abnormal signal transduction resulting in uncontrolled cell proliferation loss of apoptosis or programmed cell death tissue invasion and metastasis permitting the spread of cancer and angiogenesis leading to the enhanced blood supply of the tumor.

Biological_cause of_cancer


MECHANISM: ABNORMAL SIGNAL TRANSDUCTION

Normal cells require signals usually delivered by ligands to stimulate their growth and to tell them when to grow and when to stop growing these signals or ligands can be in the form of growth factors and inhibitors extracellular matrix component or cell adhesion molecules , these signals are transmitted into the cell through protein found on the surface of the cells called receptors,each ligand binds to its specific receptors .

Receptors often consists of three domains and extracellular ligand binding domain a transmembrane domain and an intracellular domain binding of a ligand to the extracellular domain activates the receptor tyrosine kinase which activates other protein by phosphorylation of adding a phosphate to the amino acid tyrosine on a protein inside the cell when a ligand binds to the receptor the signal goes to the intracellular domain activating the associated enzymes and initiating cascade of signal to the nucleus that tell the cell to growth and divide or to stop growing malignant cells generate many of their own growth signals which allows them to divide with reduced external growth stimulation some cells are able to produce their own growth factors and stimulate their own growth , this is called autocrine stimulation for example glioblastoma is express platelet-derived growth factors or PDGF sarcomas express tumor growth factor alpha or TGF alpha as well as epidermal growth factor receptor or EGFR .

In normal cells, the production of a cell surface receptor is limited by cellular restraints on the gene expression and protein translation. In tumor cell however mutations in the gene encoding for the receptors disrupts this finely tuned regulation and too many copies of the gene are produced a phenomenon called gene amplification. This in turns leads to the excessive transcription and production of receptors the end result is a higher then normal number of copies know as overexpression of the receptor on the tumor cell surface this give the tumor cell increased potential to be triggered into a growth phase by the binding of ligands to the excess receptor the more receptor expressed the more binding sites are available for the ligands gross overexpression of growth factor receptor can result in ligand-independent signaling where receptors are active in the absence of stimulating molecules structural changes to a receptor can also lead to ligand-independent activation for example truncated version of the epidermal growth factor receptor where much of the intercellular domain is missing are constituent’iv .

EGF receptor is also known as her1 or herb1 is a member of a subfamily of type 1 receptor tyrosine kinases these receptors are found primarily in the membrane of normal epithelial cells from skin breast colon and lung amongst other. EGF receptor and its ligands play an essential role in the regulation of cell proliferation differentiation and survival. EGFR is over-expressed in tumor arising from the colon-rectum and had a neck to name a few. When a specific ligand binds to its receptor this leads to change in the receptor that transmit a specific signal into the cell for example the receptor tyrosine kinase is activated and initiated a signaling pathway specific to that receptor this phenomenon is called signal transduction activation of a signal transduction pathway creates a complex chain of events in the cytoplasm or fluid intercellular space that eventually leads into the cell nucleus where the transcription of gene-regulating cell cycle progression are stimulated in cell proliferation one of the major cascades implicated in cancer is the rats raff mitogen-activated protein or map kinase pathway another interesting pathway is the phosphors Anozie tied 3 kinases or pi3k a kt mammalian target of rapamycin or mTOR pathway these pathways are linked to each other and another signal transduction pathway in the cell deregulation or loss of normal controls in any of this pathway is thought to be present in all human tumors .

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Once the signal reaches the nucleus transcription factor are activating these factors transcribes the genes that are translated into the protein such as growth factors that are necessary to allow the cell to continue to proliferate the end result of any growth factor receptor signal transduction pathway is tumor DNA replication and cell division one tumor cell become 2 , if mitosis continues to tumor cells become 4 with exponential growth potential on the tissue level this leads to increased tumor growth and increase tumor size many of the components of these signal transduction pathways are potential targets of the anti-cancer therapies .

Therapies can target the ligands receptors, intracellular second messengers and nuclear transcription factors responsible for tumor growth. Ligands can be neutralized before they bind to the receptors an example of this is bevacizumab or Avastin which is a humanized monoclonal antibody that targets circulating vascular endothelial growth factor or vag F platelet-derived growth factor or PDGF and fibroblast growth factor or FGF are another example of ligands that can be targeted for different cells in the body .

The receptors on the surface of normal and tumor cells can be inhibited directly sutekh Samad or Erbitux is an example of this it is a chimeric antibody that binds directly to the epidermal growth factor receptor and competitively inhibits the binding of EGF and other ligands such as TGF alpha. Another way to block the receptor is through small molecule inhibitors of receptor phosphorylation associated with them, for example, EGF receptors have a tyrosine kinase that can be blocked by the molecules gefitinib or ERISA and erlotinib or Tarceva.

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